CD8 T-cells are a major immunologic effector cell mediating resistance to cancer. Recently it has been found that CD8+ T-cells like CD4+ T-cells can be divided into two distinct subsets. By similarities with Th1 and Th2 subsets of CD4, the CD8+ T-cell subsets have been designated as Tc1 and Tc2. This division was made on the basis of the cytokines they produce. These subsets have been defined in vitro only and nothing has so far been shown regarding their distribution or function in vivo. The goal of the project proposed in this new application is to establish the existence of these subsets in vivo, to characterize their activation and functional requirements, and to determine their role in the protective immunity against transplanted malignant cells. A highly immunogenic UV-induced mouse tumor cell line has been selected as a model. Decrease in resistance to this immunogenic tumor can be observed in animals acutely treated with UV light or in advanced age. This decrease in resistance coincides with a decline in the CD8+ T-cell-mediated protective mechanisms as well as a change in cytokine production by CD8+ T-cells in response to antigenic challenge. The Tc1 response characterized by CD8+ T-cells which produce IL-2 and IFNg changes over time to a Tc2 response characterized by production of IL-4 and IL-10. This application will investigate the cause for such change, the role that the tumor may play, and whether preferential activation of Tc1 versus Tc2 in vivo correlates with protective or susceptible immunity to this tumor line.